7. Project Summary/Abstract Increasing evidence suggests that exposures from pregnancy through age 5 can result in health deficits and lead to life-long consequences. We propose to leverage and build upon a unique existing ?dual-family? adoption design to isolate early environmental exposures from heritable influences on familial clustering of health problems to contribute to ECHO's overall goal of investigating the role of early life exposures and underlying biological mechanisms in childhood health and disease. Our pediatric sample will be drawn from three cohorts of children (N = 1,201 children) who have been followed prospectively since birth in the Early Growth and Development Study (EGDS). The EGDS cohorts consist of two types of families: adoptive families in which the child is not genetically related to either rearing parent (n = 790 children), and biological families in which the child is genetically related to the rearing parent (n = 411 children). Within these families, we have n = 927 sibling pairs of two types: (1) siblings living apart, in which one sibling was adopted at birth and reared with genetically unrelated parents and the other sibling remained in the biological home and was reared by the biological parent from birth (n = 365 pairs), and (2) siblings living together either in the adoptive home or the biological home (n = 562 pairs). We have established a reliable research infrastructure, exceptional measurement of the early childhood family social environment, medical records data, DNA and salivary cortisol samples, high retention rates, and reliable and transparent data-sharing methods. We will use our well- established prospective adoption sample to (a) help clarify causal inferences about environmental influences on neurodevelopment and obesity, and (b) explore the unfolding interplay between inherited child characteristics and environmental influences from birth to adolescence. In cohorts in which children are reared by biological parents, it is difficult to differentiate the role of the social environment from that of genetic influences. Our dual-family design addresses this fundamental confound. In this application, we emphasize the Focus Area of Neurodevelopment; however, our sample and approach are also well suited for examining environmental influences on Obesity and Airways Focus Areas, as secondary and tertiary foci. In the UG3 phase, we will (1) demonstrate the feasibility of rerecruiting families into ECHO by rerecruiting and consenting families of 1,000 children; (2) prepare for the UH3 period by conducting pilot scale coding of adult medical records, piloting our geocoding system, conducting preliminary analyses, and developing and testing a brief measure of social environmental adversity; and (3) collaborate and plan with the ECHO Steering Committee. In the UH3 period, we will (1) build on the UG3 activities by enhancing our assessment of environmental and inherited risks in the EGDS cohort through in-home and phone assessments of neurodevelopment, obesity, airway function, and the social environment; and (2) conduct ECHO consortium-wide activities as determined by the ECHO Steering Committee.